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Gene’s dual role in pancreatic cancer may offer new drug target

26 April 2012

A US research team has shown how a gene known to cause pancreatic cancer when it mutates, also plays a key role in helping tumours to thrive. The discovery offers researchers a potential new target for developing drugs to fight the disease.

The Kras gene plays an important role in normal cell signalling, but can mutate to become permanently ‘switched on’, producing uncontrolled cell growth signals – and mutations in the Kras gene are seen in a large proportion of pancreatic cancer cases. Although researchers suspected that Kras also played a part in maintaining tumours, until now, it was unclear what that role was.

The new study, published in the journal Cell by researchers from the Dana-Farber Cancer Institute in Boston and Harvard Medical School, shows that Kras supports the tumour by helping to process glucose - and this provides the energy needed for the rapidly multiplying cells to grow.

The researchers used genetically engineered mice in which the Kras gene in the pancreas could be switched on and off at will. They found that when Kras was disabled, the tumours in the mice shrank by an average of 50 per cent after one week. They also noted that without Kras activity, the tumours consumed significantly less glucose, which limited their ability to grow. Since Kras regulates the activity of many genes in cells, the researchers were able to show that the enzyme pathways that are involved in processing and using glucose had been “reprogrammed” so that glucose was used to make DNA and proteins, among other things.

One of the study’s leaders, Dr Alec Kimmelman, said: "These results suggest that it may be possible to attack tumours by inhibiting some of these enzymes." However, he also cautioned that it was as yet unknown whether reducing the activity of these enzymes would have any unwanted effects on the body.

The team is now working with colleagues at the MD Anderson Cancer Centre at the University of Texas to identify possible gene targets for new drug development.